A wide variety of automated clinical analyzers are known in the art and widely used in hospitals, clinics, and research laboratories. A particularly popular example of such a device is the multi-channel type analyzer in which a series of different tests are performed simultaneously and in parallel with one another. The typical multi-channel analyzer generally utilizes liquid or solid reagents to react with a particular constituent present in a sample. Reaction parameters are then monitored using a photometric system or electrically sensitive probes to determine reaction rates, sample constituent concentrations or other similar characteristics.
The usual method employed for performing photometric procedures is to place the sample solution in a small cell, tube, or cuvette provided with transparent walls and interposing the sample solution between a light source and a photosensitive detecting element. When electrical parameters such as ion concentration are to be determined, a probe is actually immersed in the mixture of reagent and sample. In order to perform multiple tests on each sample, most contemporary multi-channel analyzers incorporate several liquid reagent storage reservoirs along with automated transfer and dispensing devices such as aspirating probes. Small aliquots of the sample are combined with the appropriate reagents and evaluated using appropriate techniques.
Although multi-channel automated analyzers incorporating liquid reagent technology have received wide acceptance, there are certain drawbacks associated with their use. For example, to repeatedly provide precise and accurate results, the liquid reagents employed in sample processing must be of consistent quality and uniform concentration. Simple mistakes or reagent degradation can render entire sample runs useless with adverse economic consequences and potentially serious results. As a result relatively labor intensive protocols must be implemented to ensure reagent consistency. Further, to maintain the necessary level of homogeneity between sample runs or reagent lots, highly trained personnel are required to operate clinical analyzers driving up the per unit test cost.
Such concerns are exacerbated by the inherent lack of stability found in a number of the reagents most useful for the analysis of biological samples. Many commonly used liquid reagents are susceptible to external environmental factors which can cause degradation of the active compound. For example, the properties of certain reagents may be altered by excessive exposure to atmospheric components such as oxygen or water. Reagents may also be degraded through exposure to light or elevated temperatures. Such degradation may lead to a reduction in reagent activity or the production of contaminating artifacts which can adversely affect sample runs.
In addition to degradation, many reagents employed in the automatic analysis of biological samples contain volatile components. In the analyzer these reagents are usually kept in temperature controlled compartments to ensure uniform sample runs. When these reagents are used in an atmospheric environment for extended periods, substantial changes in reagent concentration may occur and distort test results. Further, reagents which experience evaporation of some constituent may undergo an increase in viscosity so that they do not dispense accurately. In extreme cases, the reagent may evaporate to the point of leaving a crust of solids which blocks the dispensing mechanism used for that reagent.
Conversely, in humid or refrigerated environments the possibility of absorption or condensation of gaseous water from the operating environment may actually decrease the effective concentration of particular reagents over time. Similar additive discrepancies in reagent concentration can occur where contaminants fall or drip into the open reagent container over time.
While liquid reagent containers may be fitted with modified caps which allow the transfer of material while preventing contamination or evaporation, such caps generally interfere with reagent changing procedures and greatly increase the possibility of contamination from external sources if the closures are improperly used or switched between containers. Further, most protective caps and closures must be manually applied and correctly seated each time to operate properly. In the high volume testing environment associated with most chemical analyzers numerous reagent changes or transfers are often required within a short period of time. This greatly increases the likelihood of contamination or evaporation due to the improper use of caps or similar manual safeguards.
Like evaporation or reagent degradation, external contamination can alter the characteristics of the reagent and adversely affect sample runs. While many of the chemical analyzers currently in use have safeguards against reagent contamination built in, these protective measures may be subverted by operator error. For instance, a self cleaning probe is highly ineffective if the liquid reagent has been previously contaminated through the improper use of a screw cap from another container. Other common sources of contamination involve the transfer of bulk reagents to containers suitable for use with the analyzer and splashing between the containers during sample runs or reagent conversions.
Adding to these difficulties many liquid reagents used with automatic analyzers need to be removed daily from their temperature controlled compartment, recapped, and stored in a laboratory refrigerator due to a lack of stability. This method of storage tends to reduce reagent evaporation though it may increase the chances for reagent contamination through operator error. Further, the constant removal and change in physical environment substantially slows sample throughput and greatly increases the cost per unit test. In addition to increased labor demands, the removal and storage of reagents requires extra calibration which, though necessary, increases the time and expense of a sample run. The associated down time is also inflated by the period required for the cold reagents to re-equilibrate to stable operating temperatures. All of these potential difficulties represent significant operating interruptions and expenses that may be experienced with the operation of a clinical analyzer. More importantly, these limitations in reagent availability increase the probability of lost test results for the samples in process, as well as increasing delays in processing other specimens awaiting analysis.
Different procedures have been advanced to resolve these problems but none has proved to be a comprehensive panacea. Initially, liquid reagents were supplied in bulk form and aliquoted into volumes compatible with the analyzing apparatus. Bulk preparation of liquid reagents generally ensures consistent characteristics and reduced calibration for each assay without labor intensive mixing or cleaning. However, potential contamination problems remain and the evaporation difficulties noted above still require the daily removal of the reagents from the analyzer for controlled storage.
More recently, the liquid reagents have been provided in smaller, more convenient volumes, ready for immediate use with the analyzing equipment. Typically, these ready to use reagents are packaged in disposable vials or containers which may be resealable. Yet even if the vials or containers are resealable, the use of manually operated closures still presents several problems. For instance, the individual closure may be misplaced or inadvertently attached to the wrong container possibly contaminating the reagent within. Further, it is inconvenient to individually open and reclose each container in an automatic testing environment where test setup time and the time between tests can have a significant impact on sample throughput. In addition, the use of smaller, individually packaged reagents may increase lot to lot variation in reagents with corresponding down time for additional calibration.
Though effective at overcoming some of the earlier drawbacks associated with bulk reagents, these prior art reagent containers fail to address the need for an adaptable liquid reagent container that will ensure the stability of its contents and retard vaporization or condensation without increasing the likelihood of contamination. Such a container would enhance the ability to store liquid reagents for long periods of time on or in the chemical analyzer. With such a storage container, the analytical instrument would be continuously capable of immediately performing real time tests on biological samples. Further, such storage capabilities would increase the flexibility of the testing apparatus and substantially reduce labor costs on a per test basis. Moreover, it would be of significant benefit to the medical field and related professions to provide a fluent reagent container which reduces the level of skill necessary to effectively operate an automated processing apparatus.
Accordingly, it is an object of the present invention to provide a fluent material container which enhances the stability of stored reagents thereby maintaining the uniformity of the reagent solution over time.
It is an additional object of the present invention to provide a fluent material container which allows a reagent to be maintained in an automatic analyzer operating environment over extended periods of time without significant changes in activity.
It is yet an additional object of the present invention to provide a fluent material container which facilitates the transfer and storage of a reagent while decreasing the risk of reagent contamination.
It is a further object of the present invention to provide a fluent material container that is readily manipulated by modern automated analysis equipment thereby reducing the chance of operator error.
It is an additional object of the present invention to provide a fluent material container that is robust, simple and inexpensive to manufacture and operate, and which provides enhanced operator safety by reducing chemical exposure.